Por Dr. Henry Mauricio. Especialista en Medicina Interna
En la diabetes, al momento de indicar un medicamento, el médico tratante tomará en cuenta diferentes factores:
- Las metas establecidas
- La posibilidad real de administración
- Los efectos adversos del fármaco en cuestión
- Económicos
Estos factores ayudan no solamente con la claridad de la prescripción de una familia de fármacos, sino a escoger adecuadamente uno específico y afinar aún más los resultados con la dosis adecuada, ya que los efectos también son dosis dependientes en algunos de ellos.
Debido a los múltiples beneficios que demuestran los fármacos AR GLP1 en los campos metabólico, cardiovascular y renal, se van diseñando estudios que ponen a prueba sus efectos junto o contra placebo, metformina, sulfonilureas, insulina e incluso, otros fármacos pertenecientes a su misma familia (head-to-head). Esto ha generado una literatura tan extensa en tan pocos años, que la sola búsqueda de cada uno de los estudios es realmente extenuante. Aunado a esto, cada estudio también es llevado a formar parte de metanálisis y a discusiones, sesiones de mesas de expertos y discusiones de guías: demasiado para digerir.
A continuación, enumero los AR GLP1 y facilito sus DOI (Digital Object Identifier) o bien, sus direcciones de publicación.
- Liraglutide
- LEADER (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1603827
- ELLIPSE (Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1903822
- Dulaglutide
- AWARD-1 (Efficacy and Safety of Dulaglutide Added Onto Pioglitazone and Metformin Versus Exenatide in Type 2 Diabetes in a Randomized Controlled Trial). Publicación: https://care.diabetesjournals.org/content/37/8/2159
- AWARD-2 (Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride). Publicación: https://care.diabetesjournals.org/content/38/12/2241
- AWARD-3 (Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial). Publicación: https://care.diabetesjournals.org/content/37/8/2168
- AWARD-4 (Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/26009229
- AWARD-5 (Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/25912221
- AWARD-6 (Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60976-4/fulltext
- AWARD-7 (Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease). Publicación: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30104-9/fulltext
- AWARD-8 (A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/26799540
- AWARD-9 (Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/28294499
- AWARD-10 (Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes). Publicación: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30023-8/fulltext
- AWARD-11 (Study of the Efficacy and Safety of Investigational Dulaglutide Doses When Added to Metformin in Patients with Type 2 Diabetes Mellitus). Al momento de esta publicación, se ha reportado que los puntos de corte son satisfactorios en cuanto a lograr niveles más bajos de HbA1c a menor plazo, así como mejores valores en la pérdida de peso con las dosis de 3.0 mg y 4.5 mg de Dulaglutide semanal. Se espera que el estudio finalice a finales del 2019.
- REWIND (Dulaglutide and cardiovascular outcomes in type 2 diabetes). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext
- Albiglutide
- HARMONY (Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32261-X/fulltext
- HARMONY-2 (Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide, 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise). Publicación: https://link.springer.com/article/10.1007/s00125-015-3795-1
- HARMONY-3 (104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin). Publicación:
- HARMONY-4 (randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea). Publicación: https://link.springer.com/article/10.1007/s00125-014-3360-3
- HARMONY-5 ( year 3 results: albiglutide vs placebo and vs pioglitazone in triple therapy (background metformin and glimepiride) in people with type 2 diabetes). Este es el abstract al tercer año de estarse corriendo el estudio: https://easddistribute.m-anage.com/from.storage?image=bOIj7gcyILrLfrT9A4QWrz%2bSOSoHt9yjh91wvQFsmqK6WDEfRl7o%2fy0qPsYtR8quSHojFu2MJVTZ7sZVMx594Q%3d%3d
- HARMONY-6 (Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/24898300
- HARMONY-7 (Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs). Publicación: https://www.thelancet.com/journals/landa/article/PIIS2213-8587(13)70214-6/fulltext
- HARMONY-8 (Once Weekly GLP1 Agonist Albiglutide vs. Sitagliptin in Type 2 Diabetes Patients With Renal Impairment: Week 26 Results). Publicación: https://link.springer.com/article/10.1007/s12467-013-0029-3
- Semaglutide
- PIONEER-1 (Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes). Publicación: https://doi.org/10.2337/dc19-0749
- PIONEER-2 (Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin). Publicación: https://doi.org/10.2337/dc19-0883
- PIONEER-3 (Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea). Publicación: 10.1001/jama.2019.2942
- PIONEER-4 (Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes). Publicación: Lancet 2019;394:39-50.
- PIONEER-5 (Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment). Publicación: https://doi.org/10.1016/S2213-8587(19)30192-5
- PIONEER-6 (Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes). Publicación: https://www.nejm.org/doi/10.1056/NEJMoa1901118
- PIONEER-7 (Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes). Publicación: 10.1016/S2213-8587(19)30194-9
- PIONEER-8 (Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes). Publicación: https://doi.org/10.2337/dc19-0898
- SUSTAIN-1 (Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes). Publicación: 10.1016/S2213-8587(17)30013-X
- SUSTAIN-2 (Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes. Publicación: 10.1016/S2213-8587(17)30092-X
- SUSTAIN-3 (Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes). Publicación: 10.2337/dc17-0417
- SUSTAIN-4 (Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes). Publicación: 10.1016/S2213-8587(17)30085-2
- SUSTAIN-5 (Semaglutide Added to Basal Insulin in Type 2 Diabetes). Publicación: 10.1210/jc.2018-00070
- SUSTAIN-6 (Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1607141
- SUSTAIN-7 (Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(18)30024-X
- SUSTAIN-8 (Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(19)30311-0
- SUSTAIN-9 (Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(19)30066-X
- SUSTAIN-10 (Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes). Publicación: https://doi.org/10.1016/j.diabet.2019.101117
- SUSTAIN 11 ( Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes) Fecha estimada de finalización: 22 de febrero del 2021. datos disponibles: https://clinicaltrials.gov/ct2/show/NCT03689374
- Lixisenatide
- GetGoal-Mono (Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes). Publicación: 10.2337/dc11-1935
- GetGoal-Mono Japan (Long-term safety of once-daily lixisenatide in Japanese patients with type 2 diabetes mellitus). Publicación: 10.1016/j.jdiacomp.2015.07.003
- GetGoal-M (Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin). Publicación: 10.2337/dc12-2006
- GetGoal-M-Asia (Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea). Publicación: 10.1002/dmrr.2541
- GetGoal-F1 (Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin). Publicación: 10.1111/dme.12328
- GetGoal-P (Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone). Publicación: 10.1111/dom.12121
- GetGoal-S (Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in Type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin). Publicación: 10.1016/j.jdiacomp.2014.01.012
- GetGoal-X (Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin). Publicación: 10.2337/dc12-2709
- GetGoal-L (Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin). Publicación: 10.2337/dc12-2454
- GetGoal-Duo 1 (Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine). Publicación: 10.2337/dc12-2462
- GetGoal-L-Asia (Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea). Publicación: 10.1111/j.1463-1326.2012.01618.x
- Exenatide
- DURATION-1 (Comparison of once-weekly with twice-daily exenatide in the treatment of type 2 diabetes). Publicación: 10.1517/14656566.2010.497142
- DURATION-2 (efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once‐weekly exenatide). Publicación: https://doi.org/10.1111/j.1464-5491.2011.03301.x
- DURATION-3 (Exenatide once weekly versus insulin glargine for type 2 diabetes). Publicación: 10.1016/S2213-8587(14)70029-4
- DURATION-4 (Efficacy and Safety of Exenatide OnceWeekly Versus Metformin, Pioglitazone,and Sitagliptin Used as Monotherapy inDrug-Naive Patients With Type 2Diabetes). Publicación: https://www.researchgate.net/publication/51973878_Efficacy_and_Safety_of_Exenatide_Once_Weekly_Versus_Metformin_Pioglitazone_and_Sitagliptin_Used_as_Monotherapy_in_Drug-Naive_Patients_With_Type_2_Diabetes_DURATION-4
- DURATION-5 (Safety and tolerability of exenatide once weekly in patients with type 2 diabetes). Publicación: 10.2147/DMSO.S77290
- DURATION-6 (Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes). Publicación: 10.1016/S0140-6736(12)61267-7
- DURATION-7 (Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes). Publicación: 10.1111/dom.13266
- DURATION-8 (Hormone-substrate changes with exenatide plus dapagliflozin versus each drug alone). Publicación: 10.1111/dom.13870
Excelente recopilación de información que soporta el uso o indicación de dichos medicamentos. Gracias por tu contribución
Dr Ceron Lopez
Médico Internista
HNR/Hospital Bautista
Muy agradecido por su opinión. Todos los comentarios impulsan a mayor dedicación